Plurality of Reaction Chambers in a Test Cartridge

ABSTRACT

A fluidic testing system is presented that includes a plurality of test chambers, a plurality of inlet channels, and a fluidic network that connects the inlet channels to one or more other chambers. The plurality of test chambers are each characterized by a length and a hydraulic diameter. The length of each test chamber is aligned substantially parallel to a gravity vector. Each of the test chambers has only one opening disposed along the length of the corresponding test chamber. Additionally, each of the test chambers is coupled via its respective opening to only one of the plurality of inlet channels.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/837,007 filed on Mar. 15, 2013, which claims the benefit under 35U.S.C. §119(e) to provisional application No. 61/644,858 filed on May 9,2012, the disclosures of which are each incorporated by reference hereinin their entireties.

BACKGROUND

1. Field

Embodiments of the present invention relate to the field of clinicaldiagnostic tools.

2. Background

Given the complexity of the automation of molecular testing andimmunoassay techniques, there is a lack of products that provideadequate performances to be clinically usable in near patient testingsettings. Typical molecular testing includes various processes involvingthe correct dosage of reagents, sample introduction, lysis of cells toextract DNA or RNA, purification steps, and amplification for itssubsequent detection. Even though there are central laboratory roboticplatforms that automate some of these processes, for many testsrequiring a short turnaround time, the central laboratory cannot providethe results in the needed time requirements.

However, it is difficult to implement systems in a clinical setting thatprovide accurate, trustworthy results at a reasonable expense. Given thecomplicated nature of various molecular testing techniques, the resultsare prone to error if the testing parameters are not carefullycontrolled or if the environmental conditions are not ideal. Forexample, existing instrumentation for PCR techniques has experiencedhigh entry barriers for clinical diagnosis applications due to thebackground generated by exogenous sources of DNA. In the case ofspecific tests of pathogens, the predominant source of contamination isa result of previous reactions carried out in pipettes, tubes, orgeneral laboratory equipment. Additionally, the use of moleculartechniques for detection of microbial pathogens can produce falsenegatives. The false negatives may result from, for example: improperdisposal of agents that inhibit the Polymerase Chain Reaction (PCR) suchas hemoglobin, urine or sputum; inefficient release of DNA from cells;or low efficiency in extraction and purification of DNA or RNA.

The fact that molecular techniques have exceptional sensitivity levelsat concentrations lower than the previous reference methods makes itrather difficult to obtain clinically relevant conclusions, whileavoiding erroneous calls with false positives. To minimize this problem,especially for the detection of pathogen microorganisms, tests shouldhave quantification capability. It has therefore become increasinglynecessary to perform multiplexed assays and arrays of tests toconsolidate enough data to make confident conclusions. As an example,one of the main limitations of existing PCR-based tests is the inabilityto perform amplifications of different target genes simultaneously.While techniques such as microarrays provide very high multiplexingcapacity, their main limitation is the low speed in obtaining theresults, which often have no positive impact on patient management.

BRIEF SUMMARY

A fluidic testing system which includes a plurality of test chambers ispresented. Simultaneous fluid control of each testing site can reducetesting time and enhance the probability of obtaining repeatable resultsamong the various testing sites.

In an embodiment, a single-port fluidic testing system includes aplurality of test chambers, each characterized by a length and ahydraulic diameter. Each of the plurality of test chambers has only oneopening disposed along the length of the corresponding test chamber. Thefluidic testing system further includes a first inlet channel and aplurality of fluid splitting elements. The fluid splitting elementssplit an initial liquid flowing down the first inlet channel into aplurality of second inlet channels. Each of the plurality of testchambers is coupled via its respective opening to only one of theplurality of second inlet channels.

An example method is described. The method includes flowing an initialamount of liquid down a first inlet channel of a single-port fluidictesting system. The initial amount of liquid is split into a pluralityof second inlet channels, each second inlet channel coupled to aplurality of test chambers, wherein each of the plurality of testchambers has only one opening disposed along a length of the chamber.The method further includes filling each of the test chambers with afinal amount of liquid, the final amount being substantially equal ineach of the test chambers and summing from each test chamber to equalthe initial amount of liquid.

In another embodiment, a fluidic testing system includes a plurality oftest chambers, a plurality of inlet channels, and a fluidic network thatconnects the inlet channels to one or more other chambers. The testchambers each have a length and a hydraulic diameter. The length of eachtest chamber is aligned substantially parallel to a gravity vector. Eachof the test chambers has only one opening disposed along the length ofthe corresponding test chamber. Additionally, each of the test chambersis coupled via its respective opening to only one of the plurality ofinlet channels.

Another example method is described. The method includes flowing liquidthrough a plurality of inlet channels, each inlet channel coupled to aplurality of test chambers. A length of each test chamber is alignedsubstantially parallel to a gravity vector, and each of the testchambers has only one opening disposed along the length of the chamber.The method further includes filling each of the plurality of testchambers with the liquid up to a threshold amount. The method furtherincludes drawing the liquid away from each of the test chambers throughthe inlet channels to leave behind a predetermined amount of the liquidwithin each test chamber.

Another example method is described. The method includes flowing a firstliquid through a first inlet channel coupled to a first opening disposedalong a length of a test chamber at a first height. The length of thetest chamber is aligned substantially parallel to a gravity vector. Themethod further includes filling the test chamber with the first liquidup to a first threshold amount. The first liquid is drawn away from thetest chamber through the first inlet channel, and leaves behind a firstpredetermined amount of the first liquid within the test chamber. Themethod further includes flowing a second liquid through a second inletchannel coupled to a second opening disposed along the length of thetest chamber at a second height. The second height is greater than thefirst height. The method further includes filling the test chamber withthe second liquid up to a second threshold amount. The second liquid isdrawn away from the test chamber through the second inlet channel, andleaves behind a second predetermined amount of the second liquid withinthe test chamber.

Another example method is described. The method includes flowing liquidthrough each of a plurality of channels up to a liquid sensing areadisposed in each channel, thus setting a pre-determined amount of liquidwithin each of the plurality of channels. The method further includesflowing only the pre-determined amount of liquid within each of theplurality of channels into respective chambers coupled to each of thechannels.

BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES

The accompanying drawings, which are incorporated herein and form a partof the specification, illustrate embodiments of the present inventionand, together with the description, further serve to explain theprinciples of the invention and to enable a person skilled in thepertinent art to make and use the invention.

FIG. 1 is a graphical representation of a test cartridge system,according to an embodiment.

FIG. 2 displays a side view of the test cartridge system, according toan embodiment.

FIG. 3 illustrates a test chamber, according to an embodiment.

FIGS. 4A-C illustrate operation of the test chamber, according to anembodiment.

FIG. 5 illustrates a plurality of test chambers, according to anembodiment.

FIGS. 6A-C illustrate another operation of the test chamber, accordingto an embodiment.

FIG. 7 illustrates another test chamber, according to an embodiment.

FIG. 8 illustrates another plurality of test chambers, according to anembodiment.

FIG. 9 illustrates another plurality of test chambers, according to anembodiment.

FIG. 10 illustrates the test cartridge system within an analyzer,according to an embodiment.

FIGS. 11-14 illustrate example chamber filling methods, according toembodiments.

Embodiments of the present invention will be described with reference tothe accompanying drawings.

DETAILED DESCRIPTION

Although specific configurations and arrangements are discussed, itshould be understood that this is done for illustrative purposes only. Aperson skilled in the pertinent art will recognize that otherconfigurations and arrangements can be used without departing from thespirit and scope of the present invention. It will be apparent to aperson skilled in the pertinent art that this invention can also beemployed in a variety of other applications.

It is noted that references in the specification to “one embodiment,”“an embodiment,” “an example embodiment,” etc., indicate that theembodiment described may include a particular feature, structure, orcharacteristic, but every embodiment may not necessarily include theparticular feature, structure, or characteristic. Moreover, such phrasesdo not necessarily refer to the same embodiment. Further, when aparticular feature, structure or characteristic is described inconnection with an embodiment, it would be within the knowledge of oneskilled in the art to effect such feature, structure or characteristicin connection with other embodiments whether or not explicitlydescribed.

Embodiments described herein relate to a test cartridge system forperforming a variety of molecular tests, such as immunoassays, PCR, DNAhybridization, etc. In an embodiment, the test cartridge integrates allof the components necessary to perform such tests into a single,disposable package. The test cartridge may be configured to be analyzedby an external measurement system which provides data related to thereactions that take place within the test cartridge. In an embodiment,the test cartridge includes a plurality of test chambers with atransparent window to perform optical detection with each test chamber.

In one example, a single test cartridge may be used to perform an arrayof immunoassays with a given sample. The test cartridge contains all ofthe necessary buffers, reagents, and labels held in sealed chambersintegrated into the cartridge to perform the immunoassays.

In another example, a single test cartridge may be used to perform PCR.The DNA may be purified from the rest of a sample via a filterincorporated into the test cartridge. The sample may be extruded throughthe filter while a separately stored elution liquid may remove the DNAand bring it into another chamber to begin the process of temperaturecycling.

One of the main limitations of molecular diagnostic instrumentation isthe problem associated with contamination such as cross-contamination,carry-over contamination, etc. Embodiments described hereinsubstantially eliminate by design the contamination of samples to theinstrument.

In one embodiment, the test cartridge offers a self-contained liquidsealed during the manufacturing process. The reagents and the sample donot enter into contact with the environment or with any part of theinstrument. This feature of the test cartridge is also important formany laboratories and hospitals to safely dispose of the products aftertheir use.

In order to perform an array of tests, the test cartridge contains aplurality of test chambers designed to facilitate measuring opticalproperties of the contents within each test chamber, according to anembodiment. For example, the test chambers each contain a transparentwindow to allow for either fluorescence or absorbance studies of thecontents therein. Additionally, the design of the fluidic arrangement toeach test chamber may allow for each chamber to be filled to the samelevel while using a single pump source.

Further details relating to the components of the test cartridge system,including the test chambers, are described herein with references madeto the figures. It should be understood that the illustrations of eachphysical component are not meant to be limiting and that a person havingskill in the relevant art(s) given the description herein wouldrecognize ways to re-arrange or otherwise alter any of the componentswithout deviating from the scope or spirit of the invention.

FIG. 1 illustrates an example test cartridge system 100 with an array oftest chambers, according to an embodiment. Although reference will bemade herein to the structure of example test cartridge system 100, oneof skill in the art will recognize that test chamber embodimentsdescribed herein may be used with any number of testing system types andconfigurations.

Test cartridge system 100 includes a cartridge housing 102. Othercomponents may be considered as well for inclusion in test cartridgesystem 100, such as an analyzer module or various active components suchas pumps or heaters.

Cartridge housing 102 includes a variety of fluidic channels, chambers,and reservoirs. For example, cartridge housing 102 may include aplurality of storage chambers 116 which may contain various buffers orother reagents to be used during an assay or PCR protocol. Storagechambers 116 may be pre-filled with various liquids so that the end userwill not need to fill storage chambers 116 before placing test cartridgesystem 100 into an analyzer. In another example, the reagents arefreeze-dried before being placed in storage chambers 116. Cartridgehousing 102 may further include one or more processing chambers 124 a-bconnected to fluidic channels along a side of cartridge housing 102.Processing chambers 124 a-b may be used for a variety of processingand/or waste applications.

Samples are introduced into cartridge housing 102 via sample port 114,according to an embodiment. In an example, sample port 114 receivessolid, semi-solid, or liquid samples. In another embodiment, cartridgehousing 102 includes more than one inlet to introduce samples.

The various chambers and channels around cartridge housing 102 may besealed via the use of covers 118, 126, 127, and 128. The covers may befilms capable of sealing the fluid within cartridge housing 102. Inanother example, the covers may be plastic panels. In an example, one ormore of the covers are transparent. Additionally, one or more of thecovers may be thermally controlled for heating portions of housing 102.

The integrated test cartridge system 100 allows a user to place a sampleinto, for example, sample port 114, then place test cartridge system 100into an analyzer. In embodiments, the reaction steps to be performedincluding, for example, purification, lysing, mixing, binding, labelingand/or detecting can all be performed within test cartridge system 100via interaction with the analyzer without any need for the end user tointervene. Additionally, since all of the liquids remain sealed withintest cartridge system 100, after the test is completed, test cartridgesystem 100 may be removed from the analyzer and safely disposed ofwithout contamination of the analyzer.

FIG. 2 illustrates a side view of cartridge housing 102, according to anembodiment. The description of cartridge housing 102 is set forth todescribe features that may be present on cartridge housing 102, butshould not be limiting as to the placement or dimensional properties ofthe features.

FIG. 2 illustrates a fluidic network and a series of ports which extendinto cartridge housing 102. The fluidic network may connect to one ormore of storage chambers 116 and/or processing chambers 124 a-b ofcartridge housing 102. These chambers may be disposed on the oppositeside of cartridge housing 102 from the side illustrated in FIG. 2. In anembodiment, the fluidic network also connects to a series of testchambers 216.

Each fluidic channel may also be designed to terminate at a port whichwill interface with the ports or valve regions on a moveable transfermodule (not shown) within housing 102. A plurality of ports 210 allowfluid to flow to any chamber of housing 102, according to an embodiment.Plurality of ports 210 may act as either inlet ports for liquid to bedrawn into an inner chamber within cartridge housing 102, or as outletports for liquid to be expelled from the inner chamber to the fluidicnetwork of cartridge housing 102. For example, liquid may be pressurizedto flow through the second to the right port of liquid ports 210 anddown into the far right test chamber 216. Furthermore, liquid may bedrawn back from the far right test chamber 216 and into the second tothe right port of liquid ports 210 via an applied vacuum pressure.

Test chambers 216 may be shaped similarly, for example, to a centrifugetube. In one embodiment, liquid may be drawn into test chambers 216 tomix with reagents that have been pre-loaded into each test chamber. Forexample, each test chamber may be loaded with different primers andprobes for a PCR process, and liquid may be drawn into each test chamberto create distinct mixtures in each chamber. The reagents may befreeze-dried before being loaded into test chambers 216. In anotherembodiment, test chambers 216 are also used for sample detection.Detection may occur using an external optical source and photodetectorcoupled to an analyzer in which test cartridge system 100 is placed.Thus, any walls or covers of test chambers 216 may be transparent toallow for optical detection. In one example, the photodetector measuresabsorbance through the liquid within the test chamber at one or morewavelengths. In another example, the photodetector measures afluorescence signal generated from a fluorescent compound within thetest chamber. In an embodiment, the fluorescence measurements are takenfrom beneath test chambers 216. Test chambers 216 may be adapted forother means of detection, e.g., electrochemical, electromechanical,surface plasmon resonance, etc.

A set of smaller channel enlargements 214 are observed upstream fromtest chambers 216, according to an embodiment. Channel enlargements 214may act as liquid sensing areas. As such, channel enlargements 214 maybe used along with an external optical probe to determine whether or notliquid is present within channel enlargements 214. This determinationmay be used to activate other functions of test cartridge system 100. Inanother embodiment, channel enlargements 214 may include integratedsensors, such as a patterned resistive sensor, to indicate the presenceor flow rate of the fluid. Additionally, the optical signal detected ata particular channel enlargement 214 monitors the presence of liquidwithin a corresponding test chamber 216.

The liquid sensing areas in channel enlargements 214 may be used to setpre-determined amounts of liquid to be dosed into each test chamber 216.For example, liquid may be pressurized into each channel separately orsimultaneously until the liquid reaches the liquid sensing areas in eachchannel. In this way, each channel may contain substantially the sameamount of liquid filling the channel up to channel enlargement 214.Afterwards, each channel may be separately or simultaneously pressurizedto force the pre-determined amount of liquid down into each test chamber216, according to some embodiments.

A plurality of premixing chambers 231 may also be disposed upstream fromtest chambers 216, according to an embodiment. Premixing chambers 231may include dry chemicals, such as frozen or lyophilized analytes. Inanother example, premixing chambers 231 include dry chemistry beads orbiological samples. The biological samples may be freeze dried withinpremixing chambers 231. Such biological or chemical compounds may bestored in premixing chambers 231 for long periods of time before use.The dimensions of premixing chambers 231 may be designed to specificallyfit the size of a dry chemistry bead, usually on the order of a fewmillimeters in diameter, according to one embodiment. In one example,fluid drawn towards reaction chambers 216 mixes with the samples storedin premixing chambers 231.

At the lower part of cartridge housing 102 in FIG. 2, an optical accessarea 240 is disposed below test chambers 216, according to anembodiment. Optical access area 240 is designed to be substantiallytransparent to all wavelengths used during the optical detectionprocess. In one example, each individual test chamber 216 has its ownoptical access area. In another example, a single optical access areastretches across multiple test chambers 216.

Also illustrated on the side of cartridge housing 102 are a pressureport 236 and a vent port 234, according to an embodiment. Pressure port236 may be connected to an external pressure source for applying eitherpositive or negative pressure differentials throughout the system,according to an embodiment. Vent port 234 may either be open to theatmosphere or connect to another pressure source. For example, apositive pressure difference may be applied to one port while a negativepressure difference is applied to the other port to force a fastermovement of liquid through the coupled channels of the system.

A film or plurality of films may be placed over the series of testchambers 216. The films may be thin enough to still provide adequatesealing while also allowing for easier heating and/or cooling of thecontents within test chambers 216 via an external source. For example,the films may have a surface that is thermally controlled by any one of,or a combination of, thermoelectric devices, resistive heaters, andforced air. In one example, the films are polymeric films having athickness less than 100 microns. In one example, the thermalconductivity of the films is greater than 1 W/mK.

FIG. 3 illustrates a more detailed view of test chamber 216, accordingto an embodiment. Test chamber 216 includes a single opening 304disposed along a length of test chamber 216 that couples to an inletchannel 302. Test chamber 216 also has a curved bottom wall 306. Curvedbottom wall 306 may be transparent to allow for optical detection fromunderneath test chamber 216. Test chamber 216 has a large enoughhydraulic diameter that gravity influences the fluid flow within testchamber 216. Thus, test chamber 216 is aligned so that its length issubstantially parallel to a gravity vector. Due to this alignment, theliquid is influenced by the forces of gravity and fills the chamber fromthe bottom up.

Test chamber 216 may contain reagents 308. Any number of reagents may bepresent within reagents 308. Reagents 308 may be present in liquid formor as a freeze-dried pellet. Reagents 308 are re-suspended within theliquid that flows into test chamber 216. In another example, reagents308 are stored in premixing chamber 231 to mix with fluid upstream fromtest chamber 216.

An inlet channel 302 couples to test chamber 216 via opening 304. Inletchannel 302 may be one channel of a plurality of channels integratedwithin cartridge housing 102. Inlet channel 302 provides a fluid pathfor liquid to flow into test chamber 216 and be drawn from test chamber216.

In an embodiment, opening 304 is wider than the width of inlet channel302. The wider opening provides a more controlled entry of liquid intotest chamber 216 and also reduces the size of the droplet created by theliquid as it enters into test chamber 216 through opening 304. Each ofthese factors reduce the probability that the liquid forms a meniscusbetween the two lateral walls of test chamber 306. The formation of themeniscus makes it difficult to control the amount of liquid within thechamber and causes bubbles to form. The bubbles can disrupt anybiological processes to take place within test chamber 216 and causeerrors in the optical measurements.

An example operation of test chamber 216 is illustrated in FIGS. 4A-C,according to an embodiment. In FIG. 4A, a pre-determined amount ofliquid is disposed within inlet channel 302. The pre-determined amountof liquid is dispensed through opening 304 and into test chamber 216 asillustrated in FIG. 4B. The liquid may be dispensed, for example, via agenerated pressure difference.

In one example, the amount of liquid to be dosed into test chamber 216is chosen so that the resulting liquid level is either at or below aheight h, where h is the distance of opening 304 from the bottom of testchamber 216. The resultant liquid 402 is illustrated in FIG. 4C. As aresult, any gas in the top portion of test chamber 216 is free to escapevia opening 304.

Dosing a pre-determined amount of liquid into test chamber 216 allowsthe procedure to take place via a single pressurization event. As such,coordinating the filling of multiple test chambers in parallel issimplified.

FIG. 5 illustrates an example arrangement for a plurality of testchambers 216, according to an embodiment. A single connecting inlet (orport) 502 is illustrated for coupling the various test chambers 216 tothe fluidic network of, for example, test cartridge system 100. In anembodiment, single inlet 502 is coupled to a single port where thesingle port is the only external opening to the fluidic system.

In the example shown, since only single inlet 502 is provided for dosingliquid into multiple test chambers 216, the fluidic channels includevarious channel splitters 504 a-c. The geometry of channel splitters 504a-c may be chosen so that half of the incoming liquid flows down onepath while the other half flows down the other path. Alternatively, thegeometry may be chosen to create any ratio of splitting the liquidbetween the two resulting channels. The plurality of test chambers 216need not be aligned straight across as illustrated but can be arrangedin any fashion that keeps the total path lengths between the singleinlet 502 and each of the test chambers 216 equal. The equal pathlengths simplify the procedure for dosing controlled amounts of liquidinto each test chamber 216.

Channel splitters 504 a-c assist in providing an equal amount of liquidto dose into each of test chambers 216. For example, 80 μL of liquid maybe introduced via single connecting inlet 502. After going throughchannel splitter 504 a, 504 b, and 504 c in succession, 10 μL of liquidwould be dosed into each test chamber 216. Although this exampleconsiders that each channel splitter 504 a-c is a 50/50 fluid splitter,this does not need to be the case and any ratio of resulting fluidamounts could be realized amongst the test chambers 216.

The channel arrangement illustrated in FIG. 5 represents a closedfluidic system that allows for dosing to be more easily implemented viaa single pressurization event. For example, a positive pressure appliedto single connecting inlet 502 may be used to dose a pre-determinedamount of liquid into each of test chambers 216 as described previouslywith regard to FIGS. 4A-C.

FIGS. 6A-C describe an example operation of test chamber 216, accordingto an embodiment. In FIG. 6A, test chamber 216 is filled with liquid upto a height greater than height h. A positive pressure may be applied tofill chamber 216 up to this point. In an embodiment, a pressure sensorand/or regulator may be included with the system to control the appliedpressure and sense when the liquid has reached a threshold amount.

In FIG. 6B, a negative pressure is applied and the liquid is drawn outof test chamber 216 through inlet channel 302. The negative pressure maybe applied so that the fluid is drawn out faster than when it flowedinto test chamber 216.

In FIG. 6C, liquid is drawn out until the liquid level within testchamber 216 drops below height h. A pre-determined amount 602 of liquidremains within test chamber 216 after the negative pressure is removed.The exact volume of predetermined amount 602 depends on height h ofopening 304, the hydraulic diameter of test chamber 216, and thepressure applied during the drawing of the liquid. Using this procedure,a calculated amount of liquid can be dosed into test chamber 216 throughonly the single inlet channel 302. For example, the amount of liquidleft in the chamber may be determined by the point at which thegravitational force and surface tension on the liquid overcome thenegative pressure applied to the channel. In one example, the liquid isdrawn out of test chamber 216 quickly enough so that no reagents thatmay be present within test chamber 216 are drawn back through inletchannel 302. Height h may be adjusted for various designs of testchamber 216 to adjust the amount of liquid left behind within testchamber 216.

FIG. 7 illustrates an embodiment of a multi-channel chamber 702. Twoinlet channels 704 a-b are coupled to multi-channel chamber 702 viaopenings 706 a-b respectively. Each of openings 706 a-b are disposedalong a length of multi-channel chamber 702 at a height h₁ and h₂,respectively.

Multi-channel chamber 702 may be used to dose various controlled levelsof different liquids within the same chamber. For example, with inletchannel 704 b closed off to the atmosphere, a first liquid may flow intomulti-channel chamber 702 through inlet channel 704 a. A predeterminedamount of liquid may be dosed into multi-channel chamber 702 via inletchannel 704 a and 704 b in succession using a similar process to thatdescribed with regard to FIG. 4A-C. In another embodiment, an amount ofthe first and second liquids is left behind in multi-channel chamber 702using a similar process to that described with regard to FIGS. 6A-C. Theamount of the first liquid left behind may correspond to the height h₁of first opening 706 a. Then, inlet channel 704 a is closed off to theatmosphere while a second liquid flows into multi-channel chamber 702through inlet channel 704 b. Again, using a similar process alreadydiscussed, a predetermined amount of the second liquid is left behind inmulti-channel chamber 702. The amount of the second liquid left behindmay correspond to a difference between height h₂ and h₁ of opening 706 band 706 a respectively.

It should be appreciated that although only two inlet channels areillustrated, any number of inlet channels may be realized to deliverliquids at various heights along the length of multi-channel chamber702.

FIG. 8 illustrates a plurality of test chambers 216 as might be arrangedin cartridge housing 102, according to another embodiment. Each testchamber 216 of the plurality includes an inlet channel 302. Each inletchannel 302 may further connect to a fluidic network, such as, forexample, the fluidic network around test cartridge 102.

A single pressure source (not shown) may be coupled to the system toflow liquid down each of the plurality of inlet channels 302. Thus, eachof the plurality of test chambers 216 can be filled with the samepressure source. Additionally, during the application of a negativepressure, the same predetermined amount of fluid may be left behind ineach of the plurality of test chambers 216. The same amount of fluid maybe left in each test chamber 216 regardless of any geometricaldifferences between the various inlet channels 302, since each testchamber 216 is similarly pressurized. In another example, liquid may bepressurized into each channel up until a liquid sensing area disposed ineach channel to set a pre-determined amount of liquid in each channel,before dosing the liquid down into test chambers 216.

FIG. 9 illustrates a plurality of test chambers, according to anotherembodiment. Instead of each inlet channel 901 coupling to a singlechamber, each inlet channel 901 includes a fluidic splitter 902 todivide liquid flow into at least two split channels 903 a-b. The atleast two split channels 903 a-b may then couple to at least two testchambers 904 a-b. Although each inlet channel is depicted in FIG. 9 assplitting into two split channels 903 a-b, it would be understood by onehaving one skill in the relevant art(s) given the description herein howto split any of the inlet channels 901 into any number of otherchannels. Each of split channels 903 a-b may couple to respective testchambers 904 a-b via opening 906 a-b disposed along a length of therespective test chamber. In one example, each inlet channel 901 mayfurther connect to a fluidic network.

Feeding multiple test chambers from a fewer number of inlet channelshelps to ensure that each test chamber contains the same concentrationsof the compounds present within the liquid. Furthermore, using a singleinlet channel to dose multiple test chambers reduces the complexity ofcoupling a single pressure source to control the fluid flow to eachchamber.

FIG. 10 illustrates an analyzer 1001 that operates to perform opticaldetection of compounds within test cartridge system 100, according to anembodiment. Analyzer 1001 includes an optical probe 1002, a temperaturecontrol element 1004, a fan 1006, and a photodetector unit 1008 thatincludes an objective 1010.

Optical probe 1002 may be aligned over channel enlargement 214 to detectthe presence of liquid within the respective channel chamber. Opticalprobe 1002 may use infrared or visible light wavelengths and include anynumber of detectors and transmitter components. Additionally, the datacollected from optical probe 1002 may be used to control othercomponents of analyzer 1001. For example, after optical probe 1002 hasdetected that liquid has been present for a certain threshold period oftime, a signal may be sent to stop applying a positive pressure to theliquid and/or begin heating the contents of the test chambers of testcartridge system 100 using temperature control element 1004.

Temperature control element 1004 may be disposed near the test chambersalong the bottom portion of test cartridge system 100. Temperaturecontrol element 1004 may contain components to heat and/or cool thecontents of the test chambers. For example, temperature control element1004 may be a Peltier device that applies thermoelectric heating orcooling. In another example, temperature control element 1004 is aresistive heater. Current may be passed through coils of wire or stripsof metal printed on a surface to heat the surrounding area. In yetanother example, temperature control element 1004 provides forced air toeither heat or cool the test chambers. The forced air may be provided byfan 1006. In an embodiment, analyzer 1001 has temperature controlelements on both sides of the test chambers. One temperature controlelement may be used for heating while the other is used for cooling, forexample.

Photodetector unit 1008 may contain any type of optical detector knownto those skilled in the relevant art(s) including, but not limited to,CCD arrays, photodiodes, and CMOS sensors. In one embodiment,photodetector unit 1008 supplies an excitation wavelength of light tothe test chambers and collects the emitted fluorescence light throughobjective 1010. In another embodiment, the excitation wavelength issupplied by another source (not shown). The emitted fluorescence escapesthe test chambers via optical access area 240 along the bottom portionof the test chambers.

FIG. 11 is a flow chart illustrating a chamber filling method 1100,according to an embodiment.

At block 1102, an initial amount of liquid flows down a first inletchannel. The first inlet channel may be, for example, connecting inlet502 illustrated in FIG. 5.

At block 1104, the initial amount of liquid is split into a plurality ofsecond inlet channels, with each of the second inlet channels coupled toa plurality of test chambers. In an embodiment, each of the plurality oftest chambers has only one opening disposed along a length of thechamber for receiving one of the second inlet channels. A length of eachtest chamber may be aligned substantially parallel to a gravity vector.

At block 1106, each of the plurality of test chambers is filled with afinal amount of liquid that is substantially equal in each of the testchambers. Additionally, the final amount of liquid in each test chambersums to equal the initial amount of liquid.

Other actions may be considered as well as part of chamber fillingmethod 1100. For example, chamber filling method 1100 may includere-suspending one or more reagents disposed in one or more of theplurality of test chambers in the final amount of liquid dosed into eachof the test chambers. Another example action includes heating thecontents within at least one of the plurality of test chambers. Theheating may be performed by, for example, a Peltier device, a resistiveheating element, and/or forced air. One or more optical properties ofthe contents within at least one of the plurality of test chambers mayalso be detected during chamber filling method 1100.

FIG. 12 is a flow chart illustrating a chamber filling method 1100,according to an embodiment.

At block 1202, liquid is flown through a plurality of inlet channels.Each of the inlet channels is coupled to a plurality of test chambers,according to an embodiment. A length of each test chamber is alignedsubstantially parallel to a gravity vector. In an embodiment, each ofthe plurality of test chambers has only one opening disposed along thelength of the chamber. In one example, the flowing through the pluralityof inlet channels is performed via a single pump source.

At block 1204, each of the plurality of test chambers is filled with theliquid up to a threshold amount. In one example, the threshold amount isequal to or greater than a height at which the opening is disposed alongthe length of each of the test chambers.

At block 1206, the liquid is drawn away from each of the plurality oftest chambers through the inlet channels, leaving behind a predeterminedamount of the liquid within each test chamber. The predetermined amountof liquid may be an amount of liquid that is below the height at whichthe opening is disposed along the length of each of the test chambers.For example, the amount of liquid left in the chamber may be determinedby the point at which the gravitational force and surface tension on theliquid overcome the negative pressure applied to the channel.

Other actions may be considered as well as part of chamber fillingmethod 1200. For example, chamber filling method 1200 may includere-suspending one or more reagents disposed in one or more of theplurality of test chambers in the amount of the liquid left behindwithin the one or more test chambers. If reagents are re-suspended, thenthe drawing of liquid in block 1206 is performed quickly enough suchthat the drawn liquid does not contain the reagents. Another exampleaction includes heating the contents within at least one of theplurality of test chambers. The heating may be performed by, forexample, a Peltier device, a resistive heating element, and/or forcedair. One or more optical properties of the contents within at least oneof the plurality of test chambers may also be detected during chamberfilling method 1200.

FIG. 13 is a flow chart illustrating another chamber filling method1200, according to an embodiment.

At block 1302, a first liquid flows through a first inlet channel. In anembodiment, the first inlet channel is coupled to a first openingdisposed along a length of a test chamber at a first height. The lengthof the test chamber is aligned substantially parallel to a gravityvector. While the first liquid flows through the first inlet channel atblock 1302, a second inlet channel coupled to the test chamber is closedoff to the atmosphere. In one example, both the first and second inletchannels are open to the atmosphere to start with.

At block 1304, the test chamber is filled with the first liquid up to afirst threshold amount. In one example, the first threshold amount isequal to or greater than the first height of the first opening of thetest chamber.

At block 1306, the first liquid is drawn away from the test chamberthrough the first inlet channel, leaving behind a first predeterminedamount of liquid within the test chamber. The first predetermined amountof liquid may be an amount of liquid that corresponds to the firstheight of the first opening of the test chamber. For example, the amountof liquid left in the chamber may be determined by the point at whichthe gravitational force and surface tension on the liquid overcome thenegative pressure applied to the first channel.

At block 1308, the first inlet channel is closed off to the atmosphereand the second inlet channel is opened, according to an embodiment. Theswitching of the active channel may be performed via one or more valvescoupled to the fluidic network.

At block 1310, a second liquid flows through a second inlet channel. Inan embodiment, the second inlet channel is coupled to a second openingdisposed along the length of the test chamber at a second height that isgreater than the first height. In one example, the flowing of both thefirst liquid in block 1302 and the second liquid in block 1308 isperformed via a single pump source.

At block 1312, the test chamber is filled with the second liquid up to asecond threshold amount.

At block 1314, the second liquid is drawn away from the test chamberthrough the second inlet channel, leaving behind a second predeterminedamount of liquid within the test chamber. In one example, the secondpredetermined amount of liquid is an amount of liquid that correspondsto the difference between the second height of the second opening andthe first height of the first opening of the test chamber. In anotherexample, the amount of liquid left in the chamber may be determined bythe point at which the gravitational force and surface tension on theliquid overcome the negative pressure applied to the second channel.

Similarly to chamber filling method 1200, other actions may beconsidered as part of chamber filling method 1300. For example, chamberfilling method 1300 may include re-suspension of one or more reagentsdisposed within the test chamber in the predetermined amount of thefirst and second liquids left behind in the test chamber. Alternatively,the one or more reagents may be re-suspended in only the first liquidleft behind in the test chamber. In one example, any reagents that maybe present within the test chamber are not drawn back into either thefirst or second inlet channel in blocks 1306 and 1314 respectively.Chamber filling method 1300 may further include heating the contents ofthe test chamber and/or detecting one or more optical properties of thecontents of the test chamber as described previously in regards tochamber filling method 1200. Although only two inlet channels aredescribed in chamber filling method 1300, it should be appreciated thatchamber filling method 1300 may be expanded to include any number ofinlet channels into one or more chambers.

FIG. 14 is a flow chart illustrating another chamber filling method1400, according to an embodiment.

At block 1402, a liquid flows through each of a plurality of channels upto a liquid sensing area disposed in each channel, according to anembodiment. The liquid may be pressurized to flow down each channel, andmay be flown down each channel separately or simultaneously. Flowing theliquid up to the sensing area sets a pre-determined amount of liquidwithin each of the plurality of channels, according to an embodiment.

At block 1404, the pre-determined amount of liquid within each of theplurality of channels flows into respective chambers coupled to each ofthe channels, according to an embodiment. Each channel may be separatelyor simultaneously pressurized to force the pre-determined amount ofliquid down into each corresponding chamber.

Method 1400 may also include re-suspending one or more reagents disposedin one or more channels of the plurality of channels. The reagents maybe disposed within premixing chambers coupled to each of the channels.

The foregoing description of the specific embodiments will so fullyreveal the general nature of the invention that others can, by applyingknowledge within the skill of the art, readily modify and/or adapt forvarious applications such specific embodiments, without undueexperimentation, without departing from the general concept of thepresent invention. Therefore, such adaptations and modifications areintended to be within the meaning and range of equivalents of thedisclosed embodiments, based on the teaching and guidance presentedherein. It is to be understood that the phraseology or terminologyherein is for the purpose of description and not of limitation, suchthat the terminology or phraseology of the present specification is tobe interpreted by the skilled artisan in light of the teachings andguidance.

Embodiments of the present invention have been described above with theaid of functional building blocks illustrating the implementation ofspecified functions and relationships thereof. The boundaries of thesefunctional building blocks have been arbitrarily defined herein for theconvenience of the description. Alternate boundaries can be defined solong as the specified functions and relationships thereof areappropriately performed.

The Summary and Abstract sections may set forth one or more but not allexemplary embodiments of the present invention as contemplated by theinventor(s), and thus, are not intended to limit the present inventionand the appended claims in any way.

The breadth and scope of the present invention should not be limited byany of the above-described exemplary embodiments, but should be definedonly in accordance with the following claims and their equivalents.

What is claimed is:
 1. A method comprising: flowing liquid through aplurality of inlet channels, each inlet channel coupled to a pluralityof test chambers, wherein each of the plurality of test chambers has awall that defines a longest side of a given test chamber, and whereineach of the plurality of test chambers has only one opening through thewall of a corresponding test chamber; filling each of the plurality oftest chambers with the liquid up to a threshold amount; drawing theliquid away from each of the plurality of test chambers through theplurality of inlet channels, wherein the drawing leaves behind apredetermined amount of the liquid within each test chamber.
 2. Themethod of claim 1, further comprising re-suspending one or more reagentsdisposed in one or more of the plurality of test chambers in the amountof the liquid left behind within the one or more test chambers.
 3. Themethod of claim 2, wherein the drawing draws liquid that does notcontain the reagents.
 4. The method of claim 1, wherein filling up tothe threshold amount comprises filling each of the test chambers up to aheight equal to or greater than a height at which the opening isdisposed along the wall of each of the test chambers.
 5. The method ofclaim 4, wherein leaving behind a predetermined amount of the liquidcomprises leaving an amount of the liquid that is below the height atwhich the opening is disposed along the wall of each of the testchambers.
 6. The method of claim 1, further comprising heating thecontents within at least one of the plurality of test chambers.
 7. Themethod of claim 6, wherein the heating comprises heating with a Peltierdevice.
 8. The method of claim 6, wherein the heating comprises heatingwith resistive heating elements.
 9. The method of claim 6, wherein theheating comprises heating with forced air.
 10. The method of claim 1,further comprising detecting one or more optical properties of thecontents within at least one of the plurality of test chambers.
 11. Themethod of claim 1, wherein the flowing is performed via a single pumpsource.